Modulation of Human Myocardial Metabolism by GLP-1 Dose Response: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Modulation of Human Myocardial Metabolism by GLP-1 Dose Response (NCT01607450), a non-randomized phase 2, phase 3 study. The primary outcome is Myocardial Glucose Uptake..

2. Clinical Question

The scientific question is about a measured metabolic response, not a clinical outcome such as symptoms or cardiovascular events. The summary describes the trial as intended to generate dose-response information for later studies. It also describes comparisons of each dose with saline and a planned nonlinear curve-fitting approach to estimate sensitivity and maximal response. Whether those analyses were carried out, and their results, are not reported in the registry record.

3. Trial Design

The registry lists the study as completed, with an enrollment of 33, and identifies Indiana University as the sponsor. The recorded start is 2010-05 and the primary completion is 2012-12. The listed phases are phase 2 and phase 3. The design is described as non-randomized, single-masked, and parallel. The registry does not identify who was masked, how allocation was determined, or whether any masking was maintained throughout the study.

The interventions were saline control and three GLP-1 infusion doses. Each arm description specifies an infusion lasting 12 hours before PET. The study summary describes assessments during fasting, fatty-acid-dominant conditions. It outlines separate aims for lean healthy participants and obese participants with type 2 diabetes. For each aim, it describes four groups of 10, corresponding to saline and the three GLP-1 doses. The registry enrollment is 33, but the record does not provide a complete participant flow or explain how the stated group targets relate to enrollment and the final safety counts.

Non-randomized allocation matters when interpreting group comparisons. Differences between groups may reflect participant characteristics or allocation decisions as well as dose. Without random assignment, a saline group is not automatically a like-for-like control for a GLP-1 group. The registry record does not report allocation procedures, eligibility details, baseline comparability, or adjustments for possible confounding.

The primary outcome was measured after 12 hours of exposure. The registry also lists myocardial blood flow, myocardial total oxidation rate, cardiac index, and GLP-1 concentrations as secondary outcomes. The record does not report their results, the timing of each secondary assessment beyond the general study context, or whether all planned outcomes were analyzed. The status is completed, but completion alone does not establish that all planned analyses or participant groups were included in reported results.

4. Participant Flow and Accounting

The registry reports how participants moved through each stage of the study. All counts below are exactly as posted; missing counts are not inferred from other stages.

Only the first 6 of 7 groups are shown.

Overall Study

5. Baseline Characteristics

The table reproduces the baseline characteristics posted in the registry, which describe the participants analysed at baseline and help show whether the randomized groups were comparable.

Only the first 6 of 8 groups are shown.

6. Primary Endpoint

The registry lists the primary outcome as Myocardial Glucose Uptake., measured over After 12 hours of glucagon-like peptide 1 (GLP-1) exposure.

The primary endpoint is myocardial glucose uptake, measured in umol/min/100g after 12 hours of GLP-1 exposure. The registry states that uptake was measured using 18FDG PET and quantified with a 3-compartment model using a lumped constant of 1.0. It identifies the endpoint summary as a mean with standard deviation.

In general, myocardial glucose uptake describes the rate at which heart muscle takes up glucose. A quantitative measure can be used to compare metabolic response across dose groups and between the healthy and type 2 diabetes populations. PET provides an imaging-based way to assess tracer uptake, while the stated compartment model translates the imaging signal into an uptake estimate. These are general explanations of the measurement concepts; the registry does not give additional validation information or describe alternative measurement methods.

The endpoint was selected to address the study’s stated interest in myocardial fuel selection and GLP-1 dose response. The summary identifies glucose uptake as the primary endpoint and places measures of total oxidation and perfusion among the secondary endpoints. That distinction matters: a primary endpoint is the main prespecified outcome for evaluating the research question, while secondary measures can add context about related physiological processes. The registry record does not report the observed mean uptake, its standard deviation, confidence intervals, or a dose comparison. Therefore the magnitude and precision of any uptake response cannot be assessed from the registry information.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

The registry describes the primary measure as a continuous outcome summarized by a mean and standard deviation. General statistical interpretation of a continuous endpoint focuses on the estimated group values, the contrast between groups, and the uncertainty around that contrast. The registry record does not report those estimates for myocardial glucose uptake, nor does it give a primary analysis model or test.

What does a mean describe?

In general, a mean is a measure of the center of a distribution. It can provide a concise summary of uptake values within a group, but it does not show the full distribution or whether values are skewed, clustered, or influenced by unusual observations. The standard deviation describes the spread of individual measurements around the mean. It is not the same as the uncertainty in the estimated mean, and it does not by itself show how precisely two groups differ. The registry lists mean and standard deviation as the endpoint summary, but does not report the actual values.

How should a confidence interval be understood?

In general, a confidence interval describes the precision of an estimate under the assumptions of the statistical method used. A narrow interval indicates greater precision than a wide interval, but precision is not the same as freedom from bias. If groups are non-randomized, an interval around a contrast can reflect sampling uncertainty while leaving confounding unresolved. The registry record does not report confidence intervals for the primary endpoint.

What does the dose-response objective imply?

The study summary states that investigators intended to compare each GLP-1 dose with saline and combine data using nonlinear curve fitting to estimate sensitivity and maximal response. In general, dose-response modeling uses observations across exposure levels to describe how an outcome changes with dose. A fitted curve can summarize a pattern and estimate features of that pattern, but its reliability depends on the amount and distribution of data, the model form, and the assumptions used. The registry record does not report the fitted model, parameter estimates, uncertainty intervals, diagnostics, or whether this planned approach was completed.

Because allocation was non-randomized, modeling dose as a predictor does not by itself remove possible differences between groups. In general, an adjusted analysis can address measured covariates if they were recorded and appropriately modeled, but it cannot guarantee control of unmeasured confounding. No covariate adjustment strategy is reported in the registry record. The listed single masking does not establish how outcome assessment or analysis was protected from knowledge of group assignment; the identity of the masked party is not reported.

Why do planning calculations need careful interpretation?

General sample-size calculations estimate how many participants may be needed under specified assumptions about the effect to detect, variability, significance level, allocation, and statistical method. The registry’s planning assumptions describe an illustration based on the observed effect, two-sided significance level 0.05, equal allocation, and a normal approximation. They also specify that the targeted effect is a stated fraction of the observed effect. These assumptions are not reported as the original trial design rationale. A calculation based on an observed effect is sensitive to how precisely that effect was estimated; it does not show that the study had a given probability of detecting an effect, and it is not observed power. The registry does not report a sample-size justification for the original study.

In general, over-dispersion means that observed variability exceeds what a statistical model assumes. When that occurs, standard errors can be too small and confidence intervals too narrow if the extra variability is ignored. The registry describes a continuous endpoint and mean with standard deviation, but does not identify an analysis that assumes a count distribution or report any over-dispersion assessment. This concept is relevant only as a general example of why model assumptions matter, not as a feature established for this study.

What is known about the analysis record?

The registry record does not report the primary statistical test, a model for the primary comparison, covariate adjustments, handling of repeated or correlated measures, or analysis populations. It lists no reported analysis entries. The outcome measurement description alone is not an analysis plan: knowing how uptake was measured does not reveal how treatment groups were compared, how missing measurements were handled, or how uncertainty was calculated. These details are needed to assess whether a reported estimate would answer the stated research question and how dependent it is on modeling choices.

General statistical reading should therefore distinguish three elements: the scientific target, the numerical estimate, and the method used to quantify uncertainty. The target is myocardial glucose uptake after the specified exposure. The registry record describes that target and its measurement, but does not report the numerical estimate or its uncertainty. The method for comparing groups is also not reported. The design features—especially non-random allocation—remain relevant regardless of which statistical method was used.

10. Multiplicity, Missing Data and Analysis Populations

The study includes a primary endpoint, multiple secondary outcomes, several dose groups, and two participant populations. In general, testing many outcomes or contrasts increases the chance of finding at least one apparently notable result by chance if each is assessed independently at a conventional significance threshold. A prespecified hierarchy, adjustment procedure, or clear distinction between confirmatory and exploratory analyses can help readers understand how multiple comparisons were handled.

The registry summary describes comparisons of each GLP-1 dose with saline and a planned dose-response curve-fitting analysis. It does not report whether these analyses were performed, which comparisons were prespecified, or whether any multiplicity adjustment was used. The statistical plan for controlling or interpreting multiplicity is not reported in the registry record. Results for the secondary outcomes and analyses within each population are also not reported.

Missing-data handling is likewise not described. The registry record does not report how many participants contributed primary outcome measurements, whether any measurements were unavailable, or how missing measurements would be handled in an analysis. In general, missingness can affect interpretation when the likelihood of an unavailable measurement is related to participant characteristics or outcomes. The record does not provide enough information to assess whether missing data occurred or whether any method was used to address it.

Analysis populations are not reported in the registry record. It is therefore unclear whether analyses included all enrolled participants, only participants with measured PET outcomes, or another defined group. The record also does not describe exclusions after enrollment or protocol deviations. These omissions limit assessment of whether the analyzed groups corresponded to the planned populations and whether group comparisons could have been affected by selective inclusion.

11. Safety Results

The registry reports serious adverse events as affected participants divided by participants at risk.

Other (non-serious) adverse events

Participants with at least one non-serious event at or above the registry's 5% reporting threshold.

Most frequent non-serious adverse event terms

The adverse-event record lists serious adverse events as zero among participants at risk in the saline group and in the listed low- and mid-dose groups. The high-dose groups have zero participants recorded as at risk, so those entries do not provide an interpretable estimate of serious-event occurrence during exposure. The registry lists no serious-event terms. These figures describe the recorded safety counts; they do not establish that an event was impossible or rule out risks that a study of this size could not detect.

The record lists one non-serious adverse event in the lean group receiving 0.5 Pmol/kg/Min. It lists zero non-serious events in the other groups with participants at risk. The type of that event is not identified in the listed information. Death counts are not reported in the registry record.

In general, safety counts depend on the number of participants actually observed, the duration and completeness of follow-up, and how events were collected and classified. The adverse-event record gives group-specific at-risk counts, but the record does not explain the zero at-risk counts for the high-dose groups or provide further detail on exposure and follow-up. These data should be read as registry-reported counts, not as a comparative safety analysis. The non-randomized allocation also limits direct comparisons of event counts across groups.

12. What the Result Does, and Does Not, Mean

This study addresses a physiological question: how myocardial glucose uptake is measured after a 12-hour GLP-1 infusion at different doses, in healthy participants and participants with type 2 diabetes. Its primary endpoint is an imaging-derived metabolic measure, and the registry describes a saline control and three GLP-1 doses. This design can be relevant to developing hypotheses about myocardial metabolism and planning later research.

The registry record does not report the primary outcome values or analyses. It therefore does not establish whether uptake changed with GLP-1 exposure, whether any pattern differed by dose, or whether healthy and type 2 diabetes populations responded differently. It also does not report uncertainty around a primary effect estimate. The study objective is not itself a result, and the presence of a dose-response plan does not establish that a dose-response pattern was observed.

Even if an observed difference were available, the non-randomized allocation would need to be considered. Group differences may reflect factors associated with how participants entered or were assigned to groups. The record does not report allocation procedures, baseline comparisons, or statistical adjustments that would help evaluate this concern.

The endpoint should not be interpreted as a clinical outcome. Myocardial glucose uptake is a metabolic measure; the registry record does not report evidence about symptoms, cardiovascular events, long-term outcomes, or therapeutic benefit. The study summary describes its intended role as supporting the design of later studies evaluating therapeutic applications. That purpose is distinct from demonstrating a clinical effect.

Accordingly, the most defensible conclusion is limited: the registry describes a non-randomized study of GLP-1 dose and myocardial metabolism with a PET-based primary endpoint, but does not report the primary results needed to characterize an observed effect. No medical conclusion about treatment should be drawn from the design description or the safety counts alone.

13. Why This Trial Matters Statistically

The statistical interest of this study lies in the challenge of connecting a dose-response question to a physiological endpoint while preserving appropriate caution about design and uncertainty. The registry describes three GLP-1 doses and saline, and it identifies myocardial glucose uptake as the primary endpoint. It also describes healthy participants and participants with type 2 diabetes, creating a question about both dose and population.

Those features make transparent analysis especially important. Non-randomized allocation means that comparisons across groups may be affected by differences in participant characteristics. A numerical difference, if reported, would need to be interpreted alongside group composition, allocation procedures, and any adjustment strategy. The registry record does not report these details or the primary outcome estimates, so it cannot show how well the statistical analysis addressed the design limitations.

The stated intention to use nonlinear curve fitting also highlights a broader statistical issue: dose-response conclusions depend not only on comparing individual dose groups, but on the model used to describe the shape of the relationship. Model estimates require uncertainty reporting and assessment of fit. Without the fitted results or methods, the registry record does not permit evaluation of the estimated sensitivity, maximal response, or the adequacy of the curve.

The study also illustrates why planning calculations must be separated from observed evidence. The stated sample-size assumptions describe an illustration based on the observed effect, rather than the original trial design. Such calculations can help explore design scenarios, but cannot substitute for a prespecified rationale or demonstrate that an effect is reliable. Overall, the record raises useful questions about dose, measurement, allocation, and precision, while leaving the main statistical findings unreported.

14. Limitations

• The posted summary statistics are the only data these results rest on; patient-level data, full protocols and statistical analysis plans are not available.
• Recalculated results are simple, unadjusted calculations from posted summaries. They do not replace the sponsor's prespecified analysis.

The principal limitation for interpreting the registry record is the absence of primary outcome results. The record does not report the group means, standard deviations, contrasts, confidence intervals, or statistical tests for myocardial glucose uptake. It therefore does not permit an assessment of effect magnitude or precision.

The non-randomized design limits causal interpretation of comparisons across saline and GLP-1 groups. Allocation procedures and baseline characteristics are not reported, and no covariate adjustment strategy is described. The record does not explain who was masked or how masking was implemented. These gaps prevent a fuller assessment of possible selection bias and measurement bias.

The registry lists enrollment of 33, while its summary describes intended groups of 10 for each of two populations across saline and three dose levels. The record does not provide a complete participant flow, clarify actual group enrollment, or explain the relationship between the intended groups and recorded at-risk counts. The high-dose safety groups have zero participants at risk, but the reason is not reported.

The primary endpoint is described with a PET method and a specified compartment model, but no further information is reported about measurement quality, protocol deviations, or the handling of unavailable measurements. Analysis populations, missing-data methods, multiplicity procedures, and the statistical model used for the primary comparison are also not reported. The record lists secondary outcomes without reporting their results. These limitations leave the study’s outcome evidence and analytic robustness unclear, even though its overall research question and measurement target are identifiable.

15. Related Tutorials

16. Related Statistical Calculators

17. Sources

• ClinicalTrials.gov: Modulation of Human Myocardial Metabolism by GLP-1 Dose Response — NCT01607450.
• Registry record last updated 2016-02-17; status last verified 2016-01.
• Results first posted 2016-02-17.
• Data retrieved from ClinicalTrials.gov on 2026-11-09.
• Group sizes, means, event counts and sponsor-reported p-values are reproduced as posted. Effect estimates, confidence intervals and p-values not attributed to the sponsor are independently calculated from the posted summary statistics.

18. Record Summary

The registry describes a completed, non-randomized, single-masked, parallel study sponsored by Indiana University, with enrollment of 33 and phase listings of phase 2 and phase 3. The recorded start is 2010-05 and primary completion is 2012-12. The study concerns GLP-1 dose and myocardial metabolism in healthy participants and participants with type 2 diabetes.

Participants were assigned to saline or GLP-1 infusion groups at 0.5 pmol/kg/min, 1.5 pmol/kg/min, or 4.0 pmol/kg/min. The primary endpoint was myocardial glucose uptake after 12 hours, measured using 18FDG PET and a 3-compartment model with a lumped constant of 1.0. Secondary outcomes include myocardial blood flow, myocardial total oxidation rate, cardiac index, and GLP-1 concentrations.

The registry record does not report primary outcome results, a detailed statistical analysis plan, or a complete participant flow. Its safety entries show no recorded serious adverse events among groups with participants at risk, one non-serious event in the lean low-dose group, and no participants at risk in the high-dose groups.